Pembrolizumab Plus Y90 Radioembolization in HCC Subjects

NCT03099564 | Unknown Early Phase 1 FDA Drug FDA Device

• 1 other identifier: HCRN GI15-225
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label multi-center trial designed to evaluate the efficacy as well as the safety of combining pembrolizumab with Yttrium-90 (Y90) radioembolization in subjects with poor prognosis (high risk) HCC not eligible for liver transplant or surgical resection with well compensated liver function. Treatment will consist of pembrolizumab 200mg IV every 3 weeks in conjunction with Y90 radioembolization performed one week after the first dose of pembrolizumab. If bilobar disease is present, a second Y90 radioembolization will be performed no later than 4 weeks after the first procedure to the contralateral hepatic lobe.

Conditions

Hepatocellular Carcinoma

Keywords

Pembrolizumab; Y90 Radioembolization; KEYTRUDA®; TheraSphere®; PD-1; IgG4/kappa isotype

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Freedom from progression or death at 6 months based on RECIST 1.1 criteria

  6 months

Secondary Outcomes (4)

• Assess Safety - toxicities as defined by the NCI CTCAE v4

  2 years

• Time to progression (TTP)

  2 years

• Objective response rate (ORR)

  2 years

• Estimate overall survival (OS)

  3 years

Study Arms (1)

pembrolizumab + Y90 radioembolization

EXPERIMENTAL

Pembrolizumab 200mg IV every 3 weeks in conjunction with Y90 radioembolization (performed one week after the first dose of pembrolizumab)

Drug: Pembrolizumab; Device: Y90 radioembolization

Interventions

Pembrolizumab DRUG

pembrolizumab 200mg IV every three weeks

Also known as: Keytruda®

pembrolizumab + Y90 radioembolization

Y90 radioembolization DEVICE

The first Y90 radioembolization treatment will be administered one week after the first dose of pembrolizumab. If a second Y90 radioembolization treatment is required for bilobar disease, this should occur within 4 weeks of the initial procedure (between Cycles 2 and 3 of pembrolizumab).

pembrolizumab + Y90 radioembolization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• ECOG Performance Status of 0-1
• Locally advanced HCC as defined by: 1) tissue diagnosis OR 2) alpha-fetoprotein (AFP) \> 400 ng/mL with compatible mass on contrast-enhanced imaging OR 3) compatible mass on dual phase CT or dynamic contrast enhanced MRI demonstrating both arterial hypervascularity and delayed washout
• Hepatopulmonary shunting \< 20% as documented via hepatic artery perfusion study
• No evidence of extrahepatic metastatic disease
• Subjects must be considered poor prognosis by the following parameters: 1) right or left portal vein involvement (NOTE: subjects with main portal vein involvement are excluded), 2) multi-focal disease (more than 3 tumors regardless of size) AND/OR 3) diffuse disease considered amenable to liver directed therapy.
• Subjects with chronic infection by HCV who are untreated or who failed previous therapies for HCV are allowed on study. In addition, subjects with successful HCV treatment (defined as sustained virologic response \[SVR\] 12 or SVR 24) are allowed as long as patients are not actively receiving anti-HCV treatment at the time of study enrollment. Investigators can stop anti-HCV treatment at their discretion prior to enrolling patients on study. .
• If active HBV, viral load must be \<100IU/mL; if active HBV, subjects must be on anti-viral medication for ≥ 3 months prior to study registration and remain on the same anti-viral regimen throughout study treatment. NOTE: those subjects who are positive for Hepatitis B core antibody (anti-HBc), negative for Hepatitis B surface antigen (HBsAg) and negative for Hepatitis B surface antibody (anti-HBs), and have an HBV viral load \<100 IU/mL do not require HBV anti-viral prophylaxis.
• Not eligible for surgical resection or liver transplant or have refused such procedures.
• All disease must be amenable to embolization in one or two procedures
• Childs-Pugh Cirrhotic Status A or B with a maximum score of 7
• No evidence of clinically apparent ascites or active encephalopathy, and/or varices that have not been treated. Subjects with controlled ascites or encephalopathy are eligible so long as they meet Childs-Pugh score criterion. Please note that controlled ascites and encephalopathy require scores of 2 each when calculating the C-P score.
• No prior systemic therapy or radiotherapy (including Y90 radioembolization or cyberknife) for HCC. No prior TAE or TACE allowed. Previous liver resection and ablation therapy is permitted. Allowed prior therapies must be completed 4 weeks prior to the baseline scan, and untreated measurable disease (as per RECIST1.1) must be present.
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration:
• Hematological:

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of study registration
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy (other than oral contraceptives) or any other form of immunosuppressive therapy within 7 days prior to registration.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g.thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency.) is not considered a form of systemic treatment.
• Known history of active TB
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to registration or who has not recovered (i.e., ≤ Grade 1 or baseline) from adverse events due to agents administered \> 4 weeks prior
• Has had prior chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to registration, or who has not recovered (i.e., (i.e., ≤ Grade 1 or baseline)) from AEs due to previously administered agents
• If had major surgery, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to study registration
• Complete portal vein occlusion
• Vascular abnormalities or bleeding diathesis that indicates hepatic artery catheterization is contraindicated
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody
• Known history of HIV
• Untreated active HBV
• Dual infection with HBV/HCV or other hepatitis combinations at study entry

Sponsors & Collaborators

• Ashwin Somasundaram: lead
• Merck Sharp & Dohme LLC: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (3)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7097, United States

Location

University of Washington/Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Yu S, Yu M, Keane B, Mauro DM, Helft PR, Harris WP, Sanoff HK, Johnson MS, O'Neil B, McRee AJ, Somasundaram A. A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma. Oncologist. 2024 Mar 4;29(3):270-e413. doi: 10.1093/oncolo/oyad331.

  PMID: 38325328 DERIVED

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Ashwin Somasundaram, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 4, 2017
• Study Start: March 28, 2017
• Primary Completion: May 19, 2021
• Study Completion: June 1, 2023
• Last Updated: February 6, 2023

Record last verified: 2023-02

Locations

US (3)